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Clinical and Vaccine Immunology, April 2009, p. 444-452, Vol. 16, No. 4
1071-412X/09/$08.00+0     doi:10.1128/CVI.00405-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Oral Live Vaccine Strain-Induced Protective Immunity against Pulmonary Francisella tularensis Challenge Is Mediated by CD4+ T Cells and Antibodies, Including Immunoglobulin A{triangledown}

Heather J. Ray,1 Yu Cong,1 Ashlesh K. Murthy,1 Dale M. Selby,2 Karl E. Klose,1 Jeffrey R. Barker,1 M. Neal Guentzel,1 and Bernard P. Arulanandam1*

South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249,1 Department of Pathology, Wilford Hall Medical Centre, San Antonio, Texas 782362

Received 6 November 2008/ Returned for modification 18 December 2008/ Accepted 26 January 2009

Francisella tularensis is an intracellular gram-negative bacterium and the etiological agent of pulmonary tularemia. Given the high degrees of infectivity in the host and of dissemination of bacteria following respiratory infection, immunization strategies that target mucosal surfaces are critical for the development of effective vaccines against this organism. In this study, we have characterized the efficacy of protective immunity against pneumonic tularemia following oral vaccination with F. tularensis LVS (live vaccine strain). Mice vaccinated orally with LVS displayed colocalization of LVS with intestinal M cells, with subsequent enhanced production of splenic antigen-specific gamma interferon and of systemic and mucosal antibodies, including immunoglobulin A (IgA). LVS-vaccinated BALB/c mice were highly protected against intranasal (i.n.) SCHU S4 challenge and exhibited significantly less bacterial replication in the lungs, liver, and spleen than mock-immunized animals. Depletion of CD4+ T cells significantly abrogated the protective immunity, and mice deficient in B cells or IgA displayed partial protection against SCHU S4 challenge. These results suggest that oral vaccination with LVS induces protective immunity against i.n. challenge with F. tularensis SCHU S4 by a process mediated cooperatively by CD4+ T cells and antibodies, including IgA.

* Corresponding author. Mailing address: Department of Biology, South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, TX 78249. Phone: (210) 458-5492. Fax: (210) 458-5523. E-mail: Bernard.arulanandam{at}utsa.edu

{triangledown} Published ahead of print on 11 February 2009.

Clinical and Vaccine Immunology, April 2009, p. 444-452, Vol. 16, No. 4
1071-412X/09/$08.00+0     doi:10.1128/CVI.00405-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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